In response to RFA-AA-12-006, this application proposes the Duke Research Component of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA: DUKE) to determine the effects of alcohol use on the developing adolescent brain. Recruited at ages 12 through 21, a high risk enhanced community sample of 170 Duke subjects (N=680 from all sites) will complete a baseline assessment and undergo three annual follow-up assessments in an accelerated longitudinal design. At each visit, a multimodal magnetic resonance imaging (MRI) protocol, comprehensive neuropsychological battery, and assessments of alcohol and other substance use and related problems, mental health symptomatology, and substance use disorder risk factors will be measured. Brain imaging includes state-of-the-art high resolution structural MRI (sMRI), diffusion tensor imaging (DTI), and resting state MRI (rsMRI). The examination of alcohol consequences will focus on structural and functional maturation of brain areas that are actively developing during adolescence, involved in psychological regulation, responsive to rewards, and thought to be vulnerable to toxic alcohol effects. In addition, NCANDA: Duke will collaborate on two supplemental studies. We will collaborate with NCANDA: Pittsburgh in a study utilizing functional MRI to examine cerebral activation during a reward modulated anti-saccade task to study alcohol effects on reward responding and behavioral inhibition. We will also collaborate with NCANDA: UCSD to study a subgroup who will undergo a recovery protocol to attempt to successfully keep youth abstinent from substances for 4-6 weeks and measure recovery of neural and neurocognitive status and function. Studied in the context of risks and baseline brain characteristics, we will determine both the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent at elevated risk for an alcohol use disorder. PUBLIC HEALTH RELEVANCE: The National Consortium on Alcohol and Neurodevelopment in Adolescence (N-CANDA) will use multimodal brain imaging, neuropsychological testing and clinical assessments in a large adolescents sample followed over four years to determine neurodevelopmental risks for problematic alcohol use and alcohol effects on adolescent brain development. In addition to contributing to this goal, N-CANDA: Duke will also determine the effects of adolescent alcohol use on the neurobiological foundations of behavioral inhibition and a subgroup who will undergo a recovery protocol to attempt to successfully keep youth abstinent from substances for 4-6 weeks and measure recovery of neural and neurocognitive status and function. This information may be used to advance the prevention and treatment of adolescent alcohol use disorders.